vatalanib and everolimus in treating patients with advanced solid tumors

Conditions: Kidney Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: vatalanib and everolimus may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. purpose: this phase i trial is studying the side effects and best dose of vatalanib and everolimus and to see how well they work in treating patients with advanced solid tumors.

objectives: primary * determine the maximum tolerated dose (mtd) of vatalanib and everolimus in patients with advanced solid tumors. * determine the safety and tolerability of vatalanib and everolimus in patients with advanced solid tumors. * evaluate the safety and tolerability of vatalanib and everolimus at the mtd in patients with metastatic renal cell carcinoma (rcc). secondary * describe the non dose-limiting toxic effects associated with vatalanib and everolimus. * describe the pharmacokinetics of vatalanib and everolimus in patients with advanced solid tumors. * determine the functional extent of mtor inhibition by changes in the phosphorylation status of s6k protein in peripheral blood mononuclear cells in patients treated with vatalanib and everolimus. * describe any clinical responses seen in patients with metastatic rcc in a dose-expansion cohort treated at the mtd. * observe overall survival of rcc patients treated with vatalanib and everolimus. * determine the time to progression of patients with rcc treated with vatalanib and everolimus. outline: this is a phase i dose-escalation study followed by a phase ib study. * phase i (solid tumors): patients receive oral vatalanib on days 1-28 and oral everolimus on days 15-28 during course 1 and on days 1-28 during all subsequent courses. treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of vatalanib and everolimus until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. * phase ib (renal cell carcinoma only): patients receive oral vatalanib and oral everolimus at the mtd on days 1-28. treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. after completion of study treatment, patients are followed every 6 months. projected accrual: a total of 44 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed solid tumor with radiographic evidence of metastatic disease * no standard therapy exists (phase i) * unresectable or metastatic renal cell carcinoma (phase ib) patient characteristics: * karnofsky performance status 70-100% * absolute neutrophil count ≥ 1,500/mm³ * platelet count ≥ 100,000/mm³ * hemoglobin ≥ 9 g/dl * ast or alt ≤ 2.5 times upper limit of normal (uln) * total cholesterol \< 300 mg/dl * triglycerides \< 350 mg/dl * bilirubin ≤ 1.5 times uln * creatinine ≤ 1.5 times uln or creatinine clearance \> 40 ml/min * negative proteinuria by dip stick or total urinary protein ≤ 500 mg * no uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with antihypertensive regimen * no unstable angina pectoris * no symptomatic congestive heart failure (new york heart association class iii or iv heart disease) * no uncontrolled serious cardiac arrhythmia (symptomatic supraventricular tachycardia or any ventricular tachycardia/fibrillation) * no myocardial infarction in the past 6 months * no uncontrolled diabetes * no interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung * no active or uncontrolled infection * no uncontrolled hyperlipidemia * no chronic renal disease * no acute or chronic liver disease (e.g., hepatitis or cirrhosis) * no impaired gastrointestinal (gi) function or gi disease that may significantly alter the absorption of vatalanib or everolimus, including any of the following: * ulcerative disease * uncontrolled nausea and vomiting with solid food * watery diarrhea \> 5 times daily * malabsorption syndrome * bowel obstruction * inability to swallow the tablets * no confirmed hiv infection * not pregnant * negative pregnancy test * fertile patients must use effective contraception * no other concurrent severe and/or uncontrolled medical condition that would preclude study participation prior concurrent therapy: * recovered from prior therapy * no prior antivascular endothelial growth factor therapy * more than 4 weeks since prior major surgery\* (laparotomy) * more than 2 weeks since prior minor surgery\* * more than 4 weeks since prior chemotherapy (6 weeks for mitomycin c or nitrosoureas) * more than 6 weeks since prior antibody therapy * more than 2 weeks since prior biologic/immunotherapy * more than 2 weeks since prior limited-field radiotherapy * more than 4 weeks since prior full-field radiotherapy * more than 4 weeks since prior investigational agents * prior transfusions allowed provided blood counts are stable for \> 2 weeks * concurrent epoetin alfa allowed * no concurrent warfarin or similar oral anticoagulants that are metabolized by the cytochrome p450 system * heparin and low molecular weight heparin allowed note: \*insertion of a vascular access device is not considered major or minor surgery

Keywords: unspecified adult solid tumor, protocol specific recurrent renal cell cancer stage iv renal cell cancer